Pitfalls in mutational testing and reporting of common KIT and PDGFRA mutations in gastrointestinal stromal tumors.

BMC Med Genet 2010 Jul 4;11:106. Epub 2010 Jul 4.

Department of Pathology, University of Bonn Medical School, Sigmund-Freud-Str, 25 D-53127 Bonn, Germany.

Background: Mutation analysis of KIT and PDGFRA genes in gastrointestinal stromal tumors is gaining increasing importance for prognosis of GISTs and for prediction of treatment response. Several groups have identified specific mutational subtypes in KIT exon 11 associated with an increased risk of metastatic disease whereas GISTs with PDGFRA mutations often behave less aggressive. Furthermore, in advanced GIST disease with proven KIT exon 9 mutation the doubled daily dose of 800 mg imatinib increases the progression free survival and is now recommended both in the European and the American Guidelines. In Germany, there are still no general rules how to perform mutational analysis.

Methods: When comparing results from six different molecular laboratories we recognized the need of standardisation. Six German university laboratories with experience in mutation analysis in GISTs joined together to develop recommendations for the mutation analysis of the most common and clinically relevant hot spots, i. e. KIT exons 9 and 11 and PDGFRA exon 18. We performed a three-phased interlaboratory trial to identify pitfalls in performing molecular analysis in GISTs.

Results: We developed a design for a continuous external laboratory trial. In 2009 this external trial was conducted by 19 laboratories via the initiative for quality assurance in pathology (QuiP) of the German Society of Pathology and the Professional Association of German Pathologists.

Conclusions: By performing a three-phased internal interlaboratory trial and conducting an external trial in Germany we were able to identify potential pitfalls when performing KIT and PDGFRA mutational analysis in gastrointestinal stromal tumors. We developed standard operation procedures which are provided with the manuscript to allow other laboratories to prevent these pitfalls.

Download full-text PDF

Source
http://dx.doi.org/10.1186/1471-2350-11-106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2910708PMC
July 2010
25 Reads

Publication Analysis

Top Keywords

gastrointestinal stromal
12
mutation analysis
12
stromal tumors
12
kit pdgfra
12
external trial
8
pdgfra mutations
8
pitfalls performing
8
kit exon
8
interlaboratory trial
8
kit
6
analysis
5
trial
5
pdgfra
5
spots kit
4
analysis common
4
kit exons
4
common clinically
4
clinically relevant
4
hot spots
4
relevant hot
4

References

(Supplied by CrossRef)

M Debiec-Rychter et al.
Eur J Cancer 2006

M Heinrich et al.
J Clin Oncol 2008

E Wardelmann et al.
Virchows Arch 2007

J Lasota et al.
Histopathology 2008

M Miettinen et al.
Semin Diagn Pathol 2006

C Corless et al.
J Clin Oncol 2005

M Srinivasan et al.
Am J Pathol 2002

E Wardelmann et al.
Int J Cancer 2003

J Martin et al.
J Clin Oncol 2005

C Antonescu et al.
Clin Cancer Res 2003

J Lasota et al.
Hum Pathol 2003

Similar Publications